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34 INNOSC Theranostics and Pharmacological Sciences, 2022, Vol. 5, No. 2 Das et al.
interaction with the cell receptor. Molecular 2. Materials and methods
docking and binding affinity studies revealed the
potential of these chitosan derivatives as antiviral 2.1. Selection of monomeric and oligomeric
agents, particularly in their interaction with the subunits of chitosan derivatives
S protein of SARS-CoV-2 (Figure 1). Notably, The monomeric and oligomeric subunits of
hydroxypropyl trimethyl ammonium chloride chitosan derivatives, which exhibit improved water
chitosan (mHTCC), N,O-carboxymethyl chitosan, solubility, pH sensitivity, stability, biocompatibility,
glycerol chitosan, methyl methacrylate chitosan, and biodegradability resulting from alkylation,
monomeric chitosan, NCMC, carboxy ethyl carboxylation, acylation, and quaternization, were
chitosan, N-octadecanoyl-N-3-carboxy propionyl selected for interaction studies with the S protein
chitosan, and palmitoyl-trimethyl-chitosan of SARS-CoV-2. The decision to choose these
displayed binding affinities (ΔGb) of −6.2, −5.9, subunits was based on their reported antiviral
−4.9, −5.3, −7.9, −7.2, −6.4, and −6.9 kcal/mol, spectrum and inhibitory activity against highly
respectively. Among these, NCMC and mHTCC pathogenic human coronaviruses, as cited in
exhibited the highest binding affinities toward S Table 1. The monomeric and oligomeric subunits
protein as a polymer and monomer, respectively. include mHTCC, N,O-carboxymethyl chitosan,
Therefore, mHTCC and NCMC were selected for glycerol chitosan, methyl methacrylate chitosan,
further analysis of their protein-protein interactions monomeric chitosan, NCMC, carboxy ethyl
with the S protein-ACE2 complex. chitosan, N-octadecanoyl-N-3-carboxy propionyl
Utilizing computational methods for this study chitosan, and palmitoyl-trimethyl-chitosan.
not only reduced biological waste but also saved 2.2. Construction of 3D structures of chitosan
research time and costs. Therefore, the use of derivatives
computational approaches allowed us to explore
natural compound-based therapeutic interventions The 3D structures of chitosan and its modified
for COVID-19. The results also demonstrated the derivatives were established using their canonical
strong binding affinity of NCMC and mHTCC for smiles strings retrieved from the PubChem database
both the S protein and the RBD site of the S protein. (https://pubchem.ncbi.nlm.nih.gov/). Conversion

Figure 1. The attachment, entry, and multiplication of the severe acute respiratory syndrome coronavirus
2 in the host cell and its transport to the outer surface of the cell. Figure is generated using BioRender
software.

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